The prospect of natural gum is higher as synthetic polymers have certain disadvantages like high cost, toxicity, environmental pollution during synthesis, non-renewable and non-patient compliance etc. Hence, natural gums are widely used for conventional and novel dosage forms since these are chemically inert, non-toxic, biodegradable, non-expensive and easily available and these natural gums being modified in different ways to obtain better materials for drug delivery systems and thus can compare with available synthetic excipients. Various kinds of natural gums are used in food industry and are regarded as safe for human consumption. Gums have variety of applications in pharmacy (Prajapati, V. D., Jani, G. K., Moradiya, N. G., & Randeria, N. P. (2013). Pharmaceutical applications of various natural gums, mucilages and their modified forms. Carbohydrate polymers, 92(2), 1685-1699.). The natural gums have been studied for their application in different pharmaceutical dosage forms like matrix controlled system, film coating agents, buccal films, microspheres, nanoparticles, viscous liquid formulations like ophthalmic solutions, suspensions, implants and their applicability and efficacy has been proven. These have also been utilized as viscosity enhancers, stabilisers, disintegrants, solubilisers, emulsifiers, suspending agents, gelling agents and bioadhesives, binders in various dosage forms (Guo, J. H., Skinner, G. W., Harcum, W. W., & Barnum, P. E. (1998). Pharmaceutical applications of naturally occurring water-soluble polymers. Pharmaceutical science & technology today, 1(6), 254-261.). Exudates gums are polysaccharides produced by plants as a result of stress, including physical injury and fungal attack. Gum Arabic (Acacia senegal), gum Tragacanth (Aatragalus gummifer), gum Karaya (Sterculia urens), gum Ghatti (Anogesissus latifolia) and gum Katira (C. religiosum) have been used by humans for thousands of yeras in various food and pharmaceutical applications (Verbeken, D., Dierckx, S., & Dewettinck, K. (2003). Exudate gums: occurrence, production, and applications. Applied Microbiology and Biotechnology, 63(1), 10-21.). Natural gums have been modified to overcome certain drawbacks like uncontrolled rate of hydration, thickening, drop in viscosity on storage, solubility and microbial contamination. Various methods are available to modify the state of molecular interactions between polymers (Rana, V., Rai, P., Tiwary, A. K., Singh, R. S., Kennedy, J. F., & Knill, C. J. (2011). Modified gums: Approaches and applications in drug delivery. Carbohydrate Polymers, 83(3), 1031-1047.). Physical methods: molecular interactions between polymers can be achieved by exposure to heat, saturated steam, microwave technology and radiations. Chemical methods: polymers are treated with chemicals like aldehydes, epichlorohydrin, borex or gluteraldehyde.
Dry eye syndrome or dry eye (also known as Keratoconjuctivitis sicca) occurs when there is a problem with the tear film that normally keeps the eye moist and lubricated. It is evident from its name that Keratoconjuctivitis sicca is a drying inflammation: kerato (corneal) conjunctivitis (conjunctival inflammation) sicca (from the Latin sicco, meaning “to dry”) (Vibhute, S., Kawtikwar, P., Kshirsagar, S., & Sakarkar, D. (2010). Formulation and evaluation of tear substitutes. International Journal of Pharmaceutical Sciences Review and Research, 2, 17-20.). It is a multi-factorial disease and is accompanied by increased osmolarity of the tear film and inflammation of ocular surface. Symptoms of dry eye vary among patients, and most commonly they include itching, grittiness, burning, and sensitivity to bright light, foreign-body sensation, irritation, pain, blurred vision, and contact lens intolerance. Dry eyes can affect anyone, but it becomes more common with increasing age (Brewitt, H., & Sistani, F. (2001). Dry eye disease: the scale of the problem. Survey of ophthalmology, 45, S199-S202.). A dry eye affects about 7% people in their 50 s, and about 15% people in their 70 s. Women are affected more often than men (Lee, A. J., Lee, J., Saw, S. M., Gazzard, G., Koh, D., Widjaja, D., & Tan, D. T. H. (2002). Prevalence and risk factors associated with dry eye symptoms: a population based study in Indonesia. British Journal of Ophthalmology, 86(12), 1347-1351.). The choice of therapy for dry eye disease may be determined by the severity of the condition. Mild cases of dry eye, in which there are no signs of damage to the conjunctiva or cornea, may be successfully managed with artificial tears applied up to four times per day. In moderate cases of dry eye, examination will reveal mild damage to the cornea, such as superficial punctate keratopathy (SPK) limited to certain zones. In these cases, more frequent treatment will be required, e.g., use of unpreserved artificial tears up to 12 times per day and an unpreserved lubricating ointment at bedtime. Severe dry eye can be characterized by keratinisation of the conjunctiva and moderate to severe corneal damage, including SPK, filaments, epithelial defects, and a subsequently higher risk of secondary infections. In addition to frequent instillation of unpreserved artificial tears and lubricating ointment at night, severe cases of dry eye will require other treatment strategies, such as tear-conserving therapies (Calonge, M. (2001). The treatment of dry eye. Survey of ophthalmology, 45, S227-S239.).
Katira gum is an exudate gum, polysaccharide produced by plants as a result of stress, including physical injury and fungal attack. The gum is secreted by Cochlospermum religiosum (A small or medium sized, deciduous, soft wooded tree). The katira gum used in the present invention was purchased from “Monu Di Hatti” Kiryana store, Badala Rode, Kharar, Bill No. 521, Dated: 7 Jan. 2013. Katira gum is pale and semi-transparent, insoluble in water, but swells into a pasty transparent mass with water. The gum is sweet, thermogenic, anodyne, sedative and effective in cough, dysentery, diarrohoea, gonorrhea, syphilis, trachoma and antilice.
The heteropolysaccharide isolated from the gum (Katira) was found to consist of D-galactose, D-galactrouronic acid and L-rhamnose in a molar ratio 2:1:3 (Ojha, A. K., Maiti, D., Chandra, K., Mondal, S., Roy, D. D. S. K., Ghosh, K., & Islam, S. S. (2008). Structural assignment of a heteropolysaccharide isolated from the gum of Cochlospermum religiosum (Katira gum). Carbohydrate research, 343(7), 1222-1231).
A polysaccharide grafted katira gum was synthesized by graft acrylamide on katira gum in presence of varying concentration of cerric ammonium nitrate (CAN) as initiator. This modified gum was found to be useful as an excipient for colon targeting of drugs (Bharaniraja, B., Jayaram Kumar, K., Prasad, C. M., & Sen, A. K. (2011). Modified katira gum for colon targeted drug delivery. Journal of Applied Polymer Science, 119(5), 2644-2651; Bharaniraja, B., Kumar, K. J., Prasad, C. M., & Sen, A. K. (2011). Different approaches of katira gum formulations for colon targeting. International journal of biological macromolecules, 49(3), 305-310). The synthesis of acrylamide grafted katira gum requires a heating step at 60° C. for maximum of 5 hr on a water bath. Thus, the method proposed in the invention is microwave assisted and requires 15-20 minutes to complete the reaction process. Hence, the process proposed is considered have high industrial acceptance. A green synthesis of gold nanoparticles using aqueous solution of a hetero-polysaccharide, extracted from the katira gum and found to be useful as a efficient heterogeneous catalyst in the reduction of 4-nitrophenol to 4-aminophenol (Maity, S., Sen, I. K., & Islam, S. S. (2012). Green synthesis of gold nanoparticles using gum polysaccharide of Cochlospermum religiosum (katira gum) and study of catalytic activity. Physica E: Low-dimensional Systems and Nanostructures, 45, 130-134). Therefore, the method involves catalytic reduction of gum katira employing direct heating at 70° C. for 6 hr to prepare gold nanoparticles. However, the present invention provides microwave assisted method and requires less time to complete the reaction. The katira gum has been successfully used as a gelling agent in tissue culture media for in vitro shoot formation and rooting in Syzygium cuminii and somaic embryogenesis in Albizzia lebbeck (Jain, N., & Babbar, S. B. (2002). Gum katira—a cheap gelling agent for plant tissue culture media. Plant cell, tissue and organ culture, 71(3), 223-229).
In a different investigation methanolic extracts of leaves and flowers of Cochlospermum ereligiosum linn. was found to show antibacterial activity against eight strains of bacterial species, viz., Staphylococcus aureus, Salmonella typhi, Enterobacter aerogenes, Pseudomonas aeruginosa, Xanthomonas oryzae pv. oryzae, Xanthomonas axonopodis pv. malvacearum, Bacillus cereus and Micrococcus sp. (Bai, J. A., Rai, R. V., & Samaga, P. V. (2011). Evaluation of the antimicrobial activity of three medicinal plants of South India. Malaysian Journal of Microbiology, 7(1), 14-18). Cochlospermum religiosum is commonly called as Butter cup tree, Yellow silk cotton tree, Golden silk cotton tree is native of India, Burma and Thailand. The flowers of this tree are used for temple offerings. The synonyms of this plant are Bombax gossypium, Cochlospermum gossypium, Maximilianea gossypium. Cochlospermum religiosum is a small or medium sized, deciduous, soft wooded tree. The tree yields a gum that exudes from the fibrous, deeply furrowed bark, which is known as Katira gum (Prajapathi, N. D., Purohit, S. S., Sharma, A. K., & Kumar, T. (2003). A Handbook of medicinal plants: A complete source book. Section II, Published by Agrobios (India), Jodhpur, 27). Cochlospermum religiosum (L.) is extensively used in Ayurvedic medicines and other uses. Every part of this plant is used medicinally. It is also used for its anti-inflammatory activity in Siddha Drug ‘Kalnar Parpam’. Gum katira is used as a cheap gelling agent for plant tissue culture and has wide application in pharmaceutical and food industries. Katira gum is pale and semi-transparent, insoluble in water, but swells into a pasty transparent mass with water. This gum has assumed great importance in recent years and exported annually from India for use in the cigar paste and ice-cream industry (Ojha, A. K., Maiti, D., Chandra, K., Mondal, S., Roy, D. D. S. K., Ghosh, K., & Islam, S. S. (2008). Structural assignment of a heteropolysaccharide isolated from the gum of Cochlospermum religiosum (Katira gum). Carbohydrate research, 343(7), 1222-1231).
Carboxymethylation as well as carbamoylethylation of Cassia gum is reported to improve cold water solubility, improve viscosity and increase microbial resistance as compared to native gum (Sharma, B. R., Kumar, V., & Soni, P. L. (2003). Carbamoylethylation of Cassia tora gum. Carbohydrate polymers, 54(2), 143-147; Soni, P. L., & Sharma, P. (2000). Cassia tora gum as viscosifier and fluid loss control agent. Indian Patent Application, (680)). Therefore, Rai et al (Rai, P. R., Tiwary, A. K., & Rana, V. (2012). Superior disintegrating properties of calcium cross-linked Cassia fistula gum derivatives for fast dissolving tablets. Carbohydrate Polymers, 87(2), 1098-1104) attempted to incorporate calcium or sodium salts of carboxymethylated or carbamoylethylated C. fistula gum as superdisintegrant in the formulation development of FDTs. Thus, the present invention relates to the method of converting water insoluble, low spreadability and high swellable katira gum in to water soluble, high swellable, high spreadable carbamoylethyl katira.
Microwaves comprise electromagnetic radiation in the frequency range of 300 MHz to 300 GHz. On exposure to microwaves, the charged or polar particles tend to align themselves with electric field component of the microwaves which rapidly reverses its direction e.g. at the rate of 2.4×109/s at 2.45 GHz microwave frequency. As the polar or charged particles in a reaction medium fail to align themselves as fast as the direction of the electric field of microwaves changes, friction is created to heat the medium (Galema, S. A. (1997). Microwave chemistry. Chem. Soc. Rev., 26(3), 233-238). This heat generated could be utilized to provide activation energy for the reaction. In addition, in the microwave heating process, the high temperatures attained and the ability to work under high pressure conditions for relatively short times make reactions faster than under conventional thermal conditions, and limit the occurrence of slower side reactions. Thus, greater yields are usually obtained. (Kappe, C. O. (2004). Controlled microwave heating in modern organic synthesis. Angewandte Chemie International Edition, 43(46), 6250-6284). Hence, the present invention utilized alternative microwave assisted method to prepare carbamoylethyl katira from katira gum.
Dry eye treatment poses a substantial challenge to the clinician. The main objectives in treatment for patients with dry eye disease are to improve the patient's comfort and quality of life, and to return the ocular surface and tear film to the normal homeostatic state. Symptoms can rarely be eliminated, but they can often be improved. Eye lubricants are used to increase humidity at the ocular surface (Pinho Tavares, F. D., Fernandes, R. S., Bernardes, T. F., Bonfioli, A. A., & Carneiro Soares, E. J. (2010, May). Dry eye disease. In Seminars in ophthalmology (Vol. 25, No. 3, pp. 84-93). London, UK: Informa UK Ltd).
The extract obtained from leaves and flowers of Cochlospermum religiosum linn was found to contain alkaloids, steroids, glycosides, saponins, flavonoids, tannins and phenols. However, no reports have been available for any anti bacterial activity of gum katira. Overall, the present invention involves a process for the preparation of carbamoylethyl Katira eye lubricant solution employing microwave assistance. The technique includes use of microwave that provides reaction activation energy much faster than heating on a water bath. In addition, non uniform distribution of heating rate on water bath sometimes leads to breakage of α-(1-4) linkage present in the polysaccharides. Hence, the microwave assisted process for the synthesis of carbamoylethyl Katira eye lubricant solution is fast, safe and industrially acceptable.